-
The American Journal of Pathology Mar 1973Male wild-type mice (Cs(a) strain) were treated with ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and...
Male wild-type mice (Cs(a) strain) were treated with ethyl-alpha-p-chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug which enhances hepatic catalase synthesis and induces rapid and significant increase in the number of microbody (peroxisome) profiles in liver cells. Numerous microbody profiles, several of them appearing in clusters and retaining membranous continuities, were observed in liver cells of CPIB-treated mice. They showed a significant variation in size and configuration, and the presence or absence of the nucleoid or core did not appear to bear any relation to the size or shape of microbody profiles. Nucleoids were encountered frequently in microbody profiles measuring as small as 0.1 mu in diameter. Numerous continuities between two or more anucleoid and/or nucleoid-containing microbody profiles of different sizes and shapes were seen. These findings are inconsistent with the concept that the smaller peroxisomes are the possible precursors or progenitors of their larger counterparts. Detailed examination of numerous electron micrographs revealed irregular dilatations and tortuosities of the endoplasmic reticulum (ER) containing electron-opaque peroxisomal material displaying the characteristic appearance of matrix and usually containing irregular cores. Transitions of rough ER to smooth ER in which microbody proteins accumulated were also apparent. Numerous continuities between several microbody profiles and continuities between microbody profiles and ER are interpreted as accumulations of peroxisomal proteins in dilated tortuous channels of ER. These observations strongly suggest that the microbody proteins constitute a common pool, circulating constantly in the dilated ER channels. The size, shape and number of microbody profiles appear to reflect the amount of peroxisomal proteins present in the pool. These observations clearly suggest that the microbodies do not exist as individual entities.
Topics: Animal Feed; Animals; Clofibrate; Endoplasmic Reticulum; Liver; Male; Mice; Microbodies; Microscopy, Electron; Organoids; Proteins; Staining and Labeling
PubMed: 4120301
DOI: No ID Found -
The American Journal of Pathology Apr 1974The effects of the administration of methyl clofenapate (methyl-2-[4-(p-chlorophenyl)phenoxy]2-methylpropionate) on the inducibility of hepatic microbody (peroxisome)...
The effects of the administration of methyl clofenapate (methyl-2-[4-(p-chlorophenyl)phenoxy]2-methylpropionate) on the inducibility of hepatic microbody (peroxisome) proliferation and catalase synthesis were studied in male rats and in both sexes of wild type (Cs(a) strain) and acatalasemic (Cs(b) strain) mice. These investigations included electron microscopic examination of livers, assay of liver catalase activity, quantitation of catalase protein by immunotitration procedure, and measurements of serum cholesterol and glyceride-glycerol levels. In all groups of animals administration of methyl clofenapate at dietary concentrations of 0.015, 0.05 and 0.125% produced a significant and sustained increase in number of hepatic microbody (peroxisome) profiles. There was no appreciable increase in mitochondrial population, but several mitochondria were markedly enlarged and possessed numerous cristae. The hepatic microbody proliferation in male rats and in both sexes of wild type mice following methyl clofenapate administration was associated with a twofold increase in catalase activity and in the concentration of catalase protein. The increase in microbody population in acatalasemic mice, however, was not accompanied by a significant elevation of the catalase activity, which is due to the unusual heat lability of the mutant catalase enzyme. A marked decrease in serum cholesterol and glyceride-glycerol levels was observed in male rats following methyl clofenapate administration which paralleled the increase in liver catalase activity. In both strains of mice there was a significant reduction in serum glyceride-glycerol concentrations. All the above effects of methyl clofenapate were fully reversed when the drug was withdrawn from the diet of male wild type mice. The demonstration of microbody proliferation and catalase induction with hypolipidemic compounds, CPIB, nafenopin and, in these studies, with methyl clofenapate suggests a possible but as yet unclarified relationship between microbodies and hypolipidemia.
Topics: Animals; Biphenyl Compounds; Butyrates; Catalase; Cholesterol; Dose-Response Relationship, Drug; Endoplasmic Reticulum; Enzyme Induction; Ethers; Female; Glycerides; Glycerol; Hypolipidemic Agents; Immunoassay; Liver; Male; Mice; Microbodies; Microscopy, Electron; Mitochondria, Liver; Organ Size; Organoids; Rats
PubMed: 4825610
DOI: No ID Found -
Molecular Microbiology Aug 2004Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of... (Review)
Review
Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome.
Topics: Animals; Glycolysis; Leishmania; Microbodies; Peroxisomes; Trypanosoma
PubMed: 15255886
DOI: 10.1111/j.1365-2958.2004.04203.x -
The Journal of Biological Chemistry Feb 2022Although diabetes normally causes an elevation of cholesterol biosynthesis and induces hypercholesterolemia in animals and human, the mechanism linking diabetes to the...
Although diabetes normally causes an elevation of cholesterol biosynthesis and induces hypercholesterolemia in animals and human, the mechanism linking diabetes to the dysregulation of cholesterol biosynthesis in the liver is not fully understood. As liver peroxisomal β-oxidation is induced in the diabetic state and peroxisomal oxidation of fatty acids generates free acetate, we hypothesized that peroxisomal β-oxidation might play a role in liver cholesterol biosynthesis in diabetes. Here, we used erucic acid, a specific substrate for peroxisomal β-oxidation, and 10,12-tricosadiynoic acid, a specific inhibitor for peroxisomal β-oxidation, to specifically induce and suppress peroxisomal β-oxidation. Our results suggested that induction of peroxisomal β-oxidation increased liver cholesterol biosynthesis in streptozotocin-induced diabetic mice. We found that excessive oxidation of fatty acids by peroxisomes generated considerable free acetate in the liver, which was used as a precursor for cholesterol biosynthesis. In addition, we show that specific inhibition of peroxisomal β-oxidation decreased cholesterol biosynthesis by reducing acetate formation in the liver in diabetic mice, demonstrating a crosstalk between peroxisomal β-oxidation and cholesterol biosynthesis. Based on these results, we propose that induction of peroxisomal β-oxidation serves as a mechanism for a fatty acid-induced upregulation in cholesterol biosynthesis and also plays a role in diabetes-induced hypercholesterolemia.
Topics: Animals; Cholesterol; Diabetes Mellitus, Experimental; Fatty Acids; Hypercholesterolemia; Liver; Mice; Microbodies; Oxidation-Reduction; Peroxisomes
PubMed: 35007532
DOI: 10.1016/j.jbc.2022.101572 -
The EMBO Journal Dec 1985To determine how microbody enzymes enter microbodies, we are studying the genes for cytosolic and glycosomal (microbody) isoenzymes in Trypanosoma brucei. We have found... (Comparative Study)
Comparative Study
To determine how microbody enzymes enter microbodies, we are studying the genes for cytosolic and glycosomal (microbody) isoenzymes in Trypanosoma brucei. We have found three genes (A, B and C) coding for phosphoglycerate kinase (PGK) in a tandem array in T. brucei. Gene B codes for the cytosolic and gene C for the glycosomal isoenzyme. Genes B and C are 95% homologous, and the predicted protein sequences share approximately 45% amino acid homology with other eukaryote PGKs. The microbody isoenzyme differs from the cytosolic form and other PGKs in two respects: a high positive charge and a carboxy-terminal extension of 20 amino acids. Our results show that few alterations are required to redirect a protein from cytosol to microbody. From a comparison of our results with the unpublished data for three other glycosomal glycolytic enzymes we infer that the high positive charge represents the major topogenic signal for uptake of proteins into glycosomes.
Topics: Amino Acid Sequence; Animals; Base Sequence; Cytosol; DNA Restriction Enzymes; Genes; Humans; Isoenzymes; Microbodies; Phosphoglycerate Kinase; Sequence Homology, Nucleic Acid; Species Specificity; Trypanosoma brucei brucei
PubMed: 3004970
DOI: 10.1002/j.1460-2075.1985.tb04152.x -
Cell Feb 1996
Review
Topics: Animals; Biological Transport, Active; Cell Compartmentation; Humans; Lipid Metabolism; Microbodies; Organelles; Proteins; Signal Transduction
PubMed: 8608592
DOI: 10.1016/s0092-8674(00)81283-0 -
Physiological Reviews Jan 1998In the decade that has elapsed since the discovery of the first peroxisomal targeting signal (PTS), considerable information has been obtained regarding the mechanism of... (Review)
Review
In the decade that has elapsed since the discovery of the first peroxisomal targeting signal (PTS), considerable information has been obtained regarding the mechanism of protein import into peroxisomes. The PTSs responsible for the import of matrix and membrane proteins to peroxisomes, the receptors for several of these PTSs, and docking proteins for the PTS1 and PTS2 receptors are known. Many peroxins involved in peroxisomal protein import and biogenesis have been characterized genetically and biochemically. These studies have revealed important new insights regarding the mechanism of protein translocation across the peroxisomal membrane, the conservation of PEX genes through evolution, the role of peroxins in fatal human peroxisomal disorders, and the biogenesis of the organelle. It is clear that peroxisomal protein import and biogenesis have many features unique to this organelle alone. More recent studies on peroxisome degradation, division, and movement highlight newer aspects of the biology of this organelle that promise to be just as exciting and interesting as import and biogenesis.
Topics: Animals; Humans; Membrane Proteins; Microbodies; PHEX Phosphate Regulating Neutral Endopeptidase; Peroxisomal Disorders; Protein Biosynthesis; Protein Conformation; Proteins; Signal Transduction
PubMed: 9457172
DOI: 10.1152/physrev.1998.78.1.171 -
Cell Structure and Function Oct 1993The structurally diverse xenobiotic peroxisome proliferators (PPs) increase the number of peroxisomes per cell and the levels of several enzymes, and cause hepatomegaly,... (Review)
Review
The structurally diverse xenobiotic peroxisome proliferators (PPs) increase the number of peroxisomes per cell and the levels of several enzymes, and cause hepatomegaly, often leading to hepatocarcinogenesis in a species- and tissue-specific manner. The deadlocked problems of the molecular mechanism of PP action and its physiological meanings have begun to be understood through cDNA cloning of a PP-activated receptor (PPAR). PPAR, a member of the steroid/thyroid/vitamin superfamily of nuclear receptors, has isoforms and differentially heterodimerizes with other nuclear receptors, providing potential mechanisms not only for species- and tissue-specific actions but also for diverse actions of PPs. Recent findings related to PPAR are summarized, and its possible role in lipid metabolism and involvement in PP-induced hepatocarcinogenesis are discussed.
Topics: Amino Acid Sequence; Base Sequence; Microbodies; Molecular Sequence Data; Receptors, Cytoplasmic and Nuclear; Transcription Factors
PubMed: 8168153
DOI: 10.1247/csf.18.267 -
Journal of Lipid Research Dec 1995Recent studies refute the commonly accepted, but untested, hypothesis that 7,10,13,16-22:4 and 7,10,13,16,19-22:5 are desaturated at position 4 by a microsomal... (Review)
Review
Recent studies refute the commonly accepted, but untested, hypothesis that 7,10,13,16-22:4 and 7,10,13,16,19-22:5 are desaturated at position 4 by a microsomal acyl-CoA-dependent desaturase. The synthesis of 4,7,10,13,16,19-22:6 occurs via the following reaction sequence: 7,10,13,16,19-22:5-->9,12,15,18,21-24:5-->6,9,12,15,18,21-24:6 4,7,10,13,16,19-22:6. The synthesis of 4,7,10,13,16-22:5 from 7,10,13,16-22:4 takes place via an analogous pathway. According to these pathways the 24-carbon acids that are made in the endoplasmic reticulum move to a site for partial beta-oxidation, which is most likely peroxisomes. The products of partial beta-oxidation, 4,7,10,13,16-22:5 and 4,7,10,13,16,19-22:6, then move back to the endoplasmic reticulum where they are used as substrates for membrane lipid biosynthesis. The ability of a fatty acid to serve as a substrate for continued peroxisomal beta-oxidation, versus its transfer out of peroxisomes for subsequent endoplasmic reticulum-associated esterification reactions, may be an important control for regulating membrane lipid fatty acid composition. Indeed, the revised pathways of polyunsaturated fatty acid biosynthesis imply that there is considerable intracellular movement and recycling of fatty acids between peroxisomes and the endoplasmic reticulum. In addition, these revised pathways require that two 18-carbon and two 24-carbon acids are substrates for desaturation at position 6. Also, as linoleate and linolenate are metabolized, respectively, to 6,9,12,15,18-24:5 and 6,9,12,15,18,21-24:6, three n-6 acids and three n-3 acids are substrates for malonyl-CoA dependent chain elongation. It remains to be determined how many microsomal enzymes are required to carry out these reactions and whether other ancillary enzymes are expressed in tissues whose membrane lipids accumulate very long-chain polyunsaturated acids with up to 36 carbon atoms.
Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Fatty Acids, Unsaturated; Humans; Microbodies; Oxidation-Reduction
PubMed: 8847474
DOI: No ID Found -
Scandinavian Journal of Immunology 2007Microparticles (MP) are small membrane-bound vesicles that circulate in the peripheral blood and play active roles in thrombosis, inflammation and vascular reactivity.... (Review)
Review
Microparticles (MP) are small membrane-bound vesicles that circulate in the peripheral blood and play active roles in thrombosis, inflammation and vascular reactivity. While MP can be released from nearly every cell type, most investigation has focused on MP of platelet, leucocyte and endothelial cell origin. Cells can release MP during activation or death. Flow cytometry is the usual method to quantify MP; the small size of these structures and lack of standardization in methodology complicate measurement. As MP contain surface and cytoplasmic contents of the parent cells and bear phosphatidylserine, antibodies to specific cell surface markers and annexin V can be used for identification. Through various mechanisms, MP participate in haemostasis and have procoagulant potential in disease. MP contribute to inflammation via their influence on cell-cell interactions and cytokine release, and MP also function in mediating vascular tone. In several disease states characterized by inflammation and vascular dysfunction, MP subpopulations are elevated, correlate with clinical events, and may have important roles in pathogenesis. In the rheumatic conditions such as rheumatoid arthritis and systemic lupus erythematosus, MP are potentially important markers of disease activity and have an increasingly recognized role in immunopathogenesis. It is clear that MP play an important role in atherosclerosis, and study of these structures may provide insight into the link between chronic inflammatory conditions and accelerated atherosclerosis. As biomarkers, MP allow access to usually inaccessible tissues such as the endothelium. Further research will hopefully lead to interventions targeting MP release and function.
Topics: Animals; Female; Humans; Inflammation; Microbodies; Pregnancy; Pregnancy Complications; Thrombosis
PubMed: 17635793
DOI: 10.1111/j.1365-3083.2007.01984.x